Kaposi's sarcoma (KS) is a common AIDS-defining illness and epidemiological features suggest the involvement of a sexually transmitted agent in the etiology of AIDS-KS. The newly identified human herpesvirus-8 (HHV-8) is strongly associated in the etiology of non-AIDS and AIDS KS. Emerging serological studies suggest that seroprevalence of HHV-8 infections is low in the general U.S. population with a predominantly sexual mode of transmission. Our ongoing studies suggest that HHV-8 reactivation under reduced immuno-surveillence may precede the development of AIDS-KS. Effective future management of HHV-8 infections should incorporate control measurements such as active immunization against HHV-8. Our studies show that HHV-8 glycoproteins are good targets for human immune responses and suggest that eliciting immune response against HHV-8 envelope glycoproteins would provide an effective control against infection. Sequence data show that like other herpes viruses, HHV-8 encodes several glycoproteins. However knowledge about the identity, nature and functions of HHV-8 glycoproteins are limited and most of the available information comes from our ongoing studies. The overall objectives are to define the immunogenic envelope HHV-8 glycoproteins, to define their role in the biology of HHV-8 and to define the immune responses against them. By screening an HHV-8 cDNA library with an HIV+KS+ serum, cDNAs encoding glycoprotein gB (ORF8) and cDNAs originating from HHV-8 K8.1 gene have been identified. The K8.1 gene encodes two glycoproteins, K8.1A and B that are unique for HHV-8 and generated from spliced transcripts. Studies with human sera show that K8.1A and B are immunogenic glycoproteins. We hypothesize that ORF K8.1(A and B) and gB glycoproteins mediate important biological function(s). Our immediate focus now is to characterize the K8.1 and gB (ORF8) glycoproteins. We have formulated the following major specific aims: 1. To determine the presence and nature of K8.1(A and B) and gB glycoproteins in the infected cells and viral envelopes and to define their biochemical and structural properties. 2. To determine the role of K8.1(A and B) and gB glycoproteins in HHV-8 biology. 3. To determine the potential interactions of K8.1(A and B) and gB glycoproteins with host cell surface receptors(s) and to identify them. These studies are significant as the increased understanding of molecular, antigenic and functional characteristics of HHV-8 ORF K8.1(A and B) and gB will lead into an important in sight into the development of future control measures.